POTENTIAL ROLE OF ISORHAMNETIN TO SUPPRESS PROLIFERATION, INDUCE APOPTOSIS AND INHIBIT EMT THROUGH THE MODULATION OF PPAR¿/BMPR2 SIGNALING PATHWAYS

Abstract

GASTRIC CANCER (GC) IS A MAJOR MALIGNANCY AND THE SECOND-HIGHEST CAUSE OF DEATH DUE TO CANCER. WE EXAMINED THE ANTICANCER EFFECTS OF ISORHAMNETIN, (IH) A 3'-O-METHYLATED METABOLITE OF QUERCETIN, ON GASTRIC CANCER. USING A VIRTUAL PREDICTIVE TUMOR CELL SYSTEM, WE FOUND THAT IH COULD MODULATE VARIOUS GENES INVOLVED IN APOPTOSIS, PROLIFERATION AND ANGIOGENESIS. WE OBSERVED THAT IH INCREASED PPAR GAMMA ACTIVITY AND MODULATED THE EXPRESSION OF THE PPAR GAMMA REGULATED GENES. IH ALSO MODULATED THE EXPRESSION OF GENES THAT ARE INVOLVED IN REGULATING EPITHELIAL MESENCHYMAL TRANSITION (EMT), AND ALSO DOWNREGULATED LEVELS OF BONE MORPHOGENETIC RECEPTOR PROTEIN-2 (BMPR2) IN GASTRIC CANCER. WE FURTHER NOTED THAT IH COULD POTENTIATE THE ANTITUMOR EFFECTS OF CAPECITABINE IN A GASTRIC CANCER XENOGRAFT MOUSE MODEL. OVERALL, OUR FINDINGS CLEARLY INDICATE THAT IH EXHIBITS SIGNIFICANT ANTI-CANCER EFFECTS BOTH IN-VITRO AND IN-VIVO AND THESE ACTIONS MAY BE MEDIATED PARTIALLY THROUGH THE PPAR GAMMA ACTIVATI